The success of any pathogenic micro-organism lies in its ability to adapt to diversify, often under stressful conditions within the host. Pathogens have developed myriad ways of parallel metabolic pathways, complex regulatory systems and stress adaptive mechanisms which are best suited to the variety of environmental conditions they encounter within the human host. Organisms capable of utilizing N-acetylglucosamine (GlcNAc) as carbohydrate source are better adapted to infect and persist inside the host. The GlcNAc mutant of Candida albicans was avirulent in a murine model of systemic candidiasis (Singh, P., Ghosh, S., and Datta, A. (2001) Attenuation of virulence and changes in morphology in Candida albicans by disruption of the N-acetylglucosamine catabolic pathway. Infect Immun 69: 7898-7903). The dental plaque forming bacteria, Streptococcus sobrinus is more acidogenic than Streptococcus mutans but is less frequently isolated from human population as it is incapable of utilizing GlcNAc (Homer, K. A., Patel, R., and Beighton, D. (1993) Effects of N-acetylglucosamine on carbohydrate fermentation by Streptococcus mutans NCTC 10449 and Streptococcus sobrinus SL-1. Infect Immun 61: 295-302). The gram-negative opportunistic pathogen Bacteroides fragilis is reported to utilize N-acetyl-D-glucosamine more efficiently than glucose (Chen, H. C., Chang, C. C., Mau, W. J., and Yen L. S. (2002) Evaluation of N-acetylchitooligosaccharides as the main carbon sources for the growth of intestinal bacteria. FEMS Microbiol Lett 209: 53-56).
The gram-negative bacterium Vibrio cholerae is the causative agent of cholera, an acute dehydrating diarrhoeal disease, still endemic in many developing countries of the world. Pathogenesis of cholera involves ingestion of V. cholerae through contaminated food or water followed by its migration, after crossing the gastric acid barrier of the stomach, to the upper intestine where it has to penetrate the mucous layer for attachment to the intestinal epithelium. The bacterial growth within the host is largely dependent on the host derived macromolecules including mucin. The oligosaccharide side chains of these macromolecules are rich in amino sugars such as glucosamine and N-acetylglucosamine (GlcNAc), which can act as the source for nitrogen and carbon. Hence, it is not surprising that V. cholerae has an efficient system for the release, uptake and catabolism of these amino sugars.
Numerous enzymes are involved in the catabolization of the amino sugar, GlcNAc. In E. coli this amino sugar utilization and its regulation has been studied in detail where nagE-nagBACD are present as a divergent operon. NagC is a transcriptional regulator that represses this operon in the absence of environmental supply of amino sugars. GlcNAc catabolization converts glucosamine-6-phosphate to fructose-6-phosphate. In V. cholerae, enzymes involved in GlcNAc catabolization include β-N-acetylglucosaminidase, GlcNAc specific transporter, encoded by nagE, N-acetylglucosamine-6-phosphate deacetylase encoded by nagA1 and glucosamine-6-phosphate deaminase encoded by nagB. In V. cholera, nagA and nagC are co-transcribed and nagE is upstream of nagAC which is expressed in the opposite direction. In V. cholerae, nagE-nagAC exists as an operon but unlike E. coli, nagB is not present in the same operon. The region between nagE and nagB contains the cyclic AMP catabolic gene activator protein (CAP) binding site as well as NagC binding site (Plumbridge, J. (2001) DNA binding sites for Mlc and NagC proteins: regulation of nagE, encoding the N-acetylglucosamine transporter in Escherichia coli. Nucleic Acids Res 29: 506-514. Yamano, N., Oura, N., Wang, J., and Fujishima, S. (1997) Cloning and sequencing of the genes for N-acetylglucosamine use that construct divergent operons (nagE-nagAC) from Vibrio cholerae non-O1. Biosci Biotechnol Biochem 61: 1349-1353).
Presently, two variants of the oral vaccine for cholerae are in use, the WC-rBS and BivWC. WC-rBS, marketed as ‘Dukoral’, is a monovalent inactivated vaccine containing killed whole cells of V. cholerae O1 plus additional recombinant cholera toxin B subunit. BivWC, marketed as ‘Shanchol’ and ‘mORCVAX’, is a bivalent inactivated vaccine containing killed whole cells of V. cholerae O1 and V. cholerae O139. mORCVAX is available only in Vietnam. These oral vaccines provide protection in 52% of cases in the first year following vaccination and in 62% of cases in the second year.
There is a long felt need in the art for the inhibition and effective control of diseases caused by Vibrio spp., especially V. cholerae. Manipulation of pathogenic catabolic pathways vital for the sustenance of the pathogens in the host may prove to be an important method for the control and prevention of the pathogens.
U.S. Pat. No. 8,039,008 describes Vibrio cholerae comprising a mutated transcriptional regulatory protein (ToxT) amino acid sequence, wherein the mutation results in a reduction in the expression of cholera toxin by the Vibrio cholerae. 
U.S. Pat. No. 6,203,799 describes V. cholerae vaccine strains which have a soft agar penetration-defective phenotype and lack a functional CtxA subunit. Further, methods for identifying new genes involved in V. cholerae motility and the cloning, identification, and sequencing of V. cholerae motB and fliC genes are disclosed.
US patent application 20120045475 describes a method for inhibiting or reducing colonization by a microbial pathogen in a subject or on a surface by administering to the subject or surface an effective amount of an agent that alters the expression of a polynucleotide selected from the group consisting of rbmA, rbmB, rbmC, rbmD, rbmE, rbmF and bapl or analogues or variants thereof.
Despite the availability of vaccines against cholera, there is a dire requirement for effective prevention and control of diseases caused by V. cholerae. In the present state of art, there is a lacuna in compositions that provide effective immunity against V. cholerae mediated diseases.